الفهرس 
INTRODUCTION AND AIM OF THE WORK
Definition and PrevalenceOnly 14 pages are availabe for public view
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Abstract
Nonalcoholic fatty liver disease (NAFLD) is an important public health concern that may progress to liver fibrosis, liver cirrhosis and even hepatocellular carcinoma if not early diagnosed and treated. NAFLD also predisposes individuals to the development of T2DM and CVDs. The pathophysiological aspects of NAFLD are still incompletely understood and the available drug therapy is usually unsatisfactory.
This thesis was devoted to investigate the potential effectiveness of curcumin, the active constituent of turmeric rhizomes that possesses a wide spectrum of beneficial pharmacological properties in comparison with atorvastatin which is extensively used in the treatment of CVD, against HFD-Fed rat model of NAFLD.
In this study, NAFLD like state was induced by feeding rats with HFD composed of standard rat chow diet supplemented with 2% cholesterol and 10% lard for 16 weeks. Throughout the study, curcumin (60 mg/kg) and atorvastatin (30mg/kg) were administered daily orally either solely or concurrently to HFD-FR for 16 weeks in order to evaluate their effects on certain hallmark features of NAFLD.
Results revealed that feeding rats with HFD successfully induced NAFLD like condition as evidenced by elevation in the liver weight index, ALT level and histopathological findings in liver tissues which displayed a considerable degree of necroinflammatory injury as compared to control group. At the same time HFD-FR exhibited increase in body weight gain and visceral fat index. It also caused increase in serum TC, TGs, LDL-C levels together with decreased HDL-C levels. Besides an elevation in BGL, serum insulin level and HOMA-IR value were also recorded as compared to those of the control rat group.
Significant attenuation of these abnormalities in the assessed parameters by variable extents was observed in HFD-FR medicated with curcumin and atorvastatin either solely or in combination.
Other experiments were carried out in an attempt to explore the mechanisms underlying the evaluated effects. Data of this set of experiments indicated that the induction of NAFLD in rats was associated with an increase in MDA level alongside with decreased level of GPx. These results clearly demonstrated the increase in oxidative stress in these HFD-FR. In addition HFD-FR exhibited increased levels of proinflammatory parameters, TNF-α and CRP alongside with decreased level of anti-inflammatory adipokine, adiponectin .
Importantly, induction of NAFLD in rats was associated with reduced expression of hepatic PPAR-α.
Treatment of HFD-FR with curcumin and/or atorvastatin led to improvement of oxidative stress parameters as evidenced by a decrease in the elevated levels of MDA and increase in the level of GPx.
The two drugs in question caused significant reduction in the levels of TNF-α and CRP together with elevation in adiponectin level indicating their anti-inflammatory activities.
Importantly, treatment of HFD-FR with curcumin or atorvastatin either singly or concurrently induced upregulation of the expression of hepatic PPAR-α.
Interestingly, throughout this study, curcumin seems to be fairly comparable or oftenly slightly superior to atorvastatin in alleviation the abnormalities associated with the induction of NAFLD in rats-fed HFD.
In addition, the efficacy of each curcumin and atorvastatin was augmented upon their combination. Thus, most features of NAFLD in HFD-FR not only improved, but seem even to be normalized when the two drugs were concurrently administered. The enhancement of their efficacies upon their combination might be relevant to their complementary mechanisms of action.
In conclusion, the findings of the present study in HFD-Fed rat model of NAFLD suggested that curcumin-atorvastatin combination might represent a potential therapeutic approach for NAFLD as their effectiveness were augmented upon their coadministration. The amelioration of NAFLD abnormalities offered by curcumin, atorvastatin and their combination is possibly mechanistically relevant to their abilities to reduce oxidative stress and to improve the inflammatory status and also their capabilities to repair downregulation of the hepatic PPAR-α expression. However, other possible mechanisms cannot be ruled out and further studies are still required to clarify this point. Lastly, the important findings demonstrated in the present study in a rat model of NAFLD encourage further confirmatory clinical studies in the near future to substantiate the use of curcumin-atorvastatin combination as a therapeutic approach for NAFLD.